This application is a 371 of International Application No. PCT/IB98/02065, filed Dec. 18, 1998, which claims the benefit of International Application No. PCT/IB98/00003, filed Jan. 5, 1998.
This invention relates to novel 2,3-substituted indoles as pharmaceutical agents. This invention specifically relates to compounds, compositions and methods for the treatment or alleviation of pain and inflammation and other inflammation-associated disorders, such as arthritis.
Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in treating pain and the signs and symptoms of arthritis because of their analgesic and anti-inflammatory activity. It is accepted that common NSAIDs work by blocking the activity of cyclooxygenase (COX), also known as prostaglandin G/H synthase (PGHS), the enzyme that converts arachidonic acid into prostanoids. Prostaglandins, especially prostaglandin E2 (PGE2), which is the predominant eicosanoid detected in inflammation conditions are mediators of pain, fever and other symptoms associated with inflammation. Inhibition of the biosynthesis of prostaglandins has been a therapeutic target of anti-inflammatory drug discovery. The therapeutic use of conventional NSAIDs is, however, limited due to drug associated side effects, including life threatening ulceration and renal toxicity. An alternative to NSAIDs is the use of corticosteriods, however, long term therapy can also result in severe side effects.
Recently, two forms of COX were identified, a constitutive isoform (COX-1) and an inducible isoform (COX-2) of which expression is upregulated at sites of inflammation (Vane, J. R.; Mitchell, J. A.; Appleton, I.; Tomlinson, A.; Bishop-Bailey, D.; Croxtoll, J.; Willoughby, D. A. Proc. Natl. Acad Sci. USA, 1994, 91, 2046). COX-1 is thought to play a physiological role and to be responsible for gastrointestinal and renal protection. On the other hand, COX-2 appears to play a pathological role and to be the predominant isoform present in inflammation conditions. A pathological role for prostaglandins has been implicated in a number of human disease states including rheumatoid and osteoarthritis, pyrexia, asthma, bone resorption, cardiovascular diseases, nephrotoxicity, atherosclerosis, hypotension, shock, pain, cancer, and Alzheimer disease. The NSAIDs currently on market inhibit both isoforms of COX with little variation for selectivity, explaining their beneficial (inhibition of COX-2) and deleterious effects (inhibition of COX-1). It is believed that compounds that would selectively inhibit the biosynthesis of prostaglandins by intervention of the induction phase of the inducible enzyme cyclooxygenase-2 and/or by intervention of the activity of the enzyme cyclooxygenase-2 on arachidonic acid would provide alternate therapy to the use of NSAIDs or corticosteriods in that such compounds would exert anti-inflammatory effects without the adverse side effects associated with COX-1 inhibition.
A variety of indole compounds are known and are disclosed in several patent applications. The International Publication Numbers WO 96/32379 discloses N-substituted indole compounds as cGMP-PDE Inhibitors. The International Publication Numbers WO 96/37467, WO 96/37469, UK Patent Publication GB 2283745 A and U.S. Pat. No. 5,510,368 disclose 2-methyl-N-substituted indole compounds as cyclooxygenase-2 Inhibitors. Also, a variety of indole compounds are disclosed as agents for controlling underwater fouling organisms in European Patent Publication Number 0 556 949 A2 by Konya, Kazumi et. al. Specifically, the International Publication Numbers WO 97/09308 discloses indole compounds as neuropeptide receptor antagonists. Besides, in Sci. Pharm. 64, 577 (1996), a process for preparing a 2-ester-substituted indoline is disclosed.
The present invention provides a compound of the following formula: 
or the pharmaceutically acceptable salts thereof wherein
Z is OH, C1-6 alkoxy, xe2x80x94NR2R3 or a group of the formula (II) or (III): 
wherein r is 1, 2, 3 or 4, Y is a direct bond, O, S or NR4, and W is OH or xe2x80x94NR2R3;
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R1 is hydrogen, C1-4 alkyl or halo;
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
R4 is hydrogen or C1-4 alkyl;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, 3 or 4.
The indole compounds of the present invention exhibit inhibition of COX activity. Preferably compounds of this invention exhibit inhibitory activity against COX-2, with more preferable compounds having COX-2 selectivity.
Accordingly, the present invention also provides a pharmaceutical composition, useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens, which comprises a compound of the formula (I) and the pharmaceutically acceptable salts thereof.
Further, the present invention provides a method for the treatment of a medical condition in which prostaglandins are implicated as pathogens, in a mammalian subject, which comprises administering to said subject a therapeutically effective amount of said pharmaceutical composition.
The medical conditions in which prostaglandins are implicated as pathogens, include the relief of pain, fever and inflammation of a variety of conditions including rheumatic fever, symptoms associated with influenza or other viral infections, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, myositis, neuralgia, synovitis, arthritis including rheumatoid arthritis, degenerative joint disease (osteoarthritis), gout, ankylosing spondylitis, systemic lumpus erythematosus and juvenile arthritis, bursitis, burns, injuries following surgical and dental procedures.
The compounds and pharmaceutical composition of this invention may inhibit cellular neoplastic transformations and metastatic tumor growth and thus may be used in the treatment and/or prevention of cancers in the colon, breast, skin, esophagus, stomach, urinary bladder, lung and liver. The compounds and pharmaceutical composition of this invention were used in the treatment and/or prevention of cyclooxygenase-mediated proliferation disorders such as which occur in diabetic retinopathy and tumor angiogenesis.
The compounds and pharmaceutical composition of this invention may inhibit prostaniod-induced smooth muscle contraction by preventing the synthesis of contractile prostanoids, and thus may be of use in the treatment of dysmenorrhea, premature labor, asthma and eosinophil related disorders and in the treatment of neurodegenerative diseases such as Alzheimer""s and Parkinson""s disease, and for the treatment of bone loss (treatment of osteoarthritis), stroke, seizures, migraine, multiple sclevosis, AIDS and encephaloathy.
By virtue of the COX-2 activity and/or specificity for COX-2 over COX-1, such compounds will prove useful as an alternative to conventional NSAIDs particularly where such NSAIDs may be contra-indicated such as in patients with ulcers (such as peptic ulcers and gastric ulcers), gastritis, regional enterotis, ulcerative colitis, diverticulitis or with a recurrent history of GI lesions, GI bleeding, coagulation disorders including anemia such as hypoprothrombinemia, haemophilia and other bleeding problems; kidney disease; prior to surgery of taking of anticoagulants.
Also, the present invention provides a compound of formula 7-VI: 
wherein B is a suitable protecting group;
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; R5 is C1-6 alkyl; and
n is 0, 1, 2, 3 or 4.
Also, the present invention provides a compound of formula 7-V: 
wherein B is a suitable protecting group;
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; R5 is C1-6 alkyl; and
n is 0, 1, 2, 3 or 4.
As used herein, xe2x80x9chaloxe2x80x9d is fluoro, chloro, bromo or iodo.
As used herein, the term xe2x80x9cC1-4 alkylxe2x80x9d means straight or branched chain saturated radicals of 1 to 4 carbon atoms, including, but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and the like.
As used herein, an example of xe2x80x9cpropylxe2x80x9d is n-propyl and isopropyl.
As used herein, an example of xe2x80x9cbutylxe2x80x9d is n-butyl, isobutyl, sec-butyl and tert-butyl.
As used herein, an example of xe2x80x9calkoxyxe2x80x9d is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, and the like.
As used herein, an example of xe2x80x9calkylthioxe2x80x9d is methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, and the like.
As used herein, an example of xe2x80x9cdi-(C1-4 alkyl)aminoxe2x80x9d is dimethylamino, diethylamino, dipropylamino, N-methyl-N-ethylamino, N-methyl-N-propylamino, N-methyl-N-butylamino, N-ethyl-N-propylamino, and the like.
As used herein, an example of xe2x80x9cC1-4 alkylaminoxe2x80x9d is methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino, and the like.
As used herein, an example of xe2x80x9cHOxe2x80x94(C1-4)alkylxe2x80x9d is hydroxymethyl, hydroxyethyl (e.g., 1-hydroxyethyl and 2-hydroxyethyl), hydroxypropyl (e.g., 1-hydroxypropyl, 2-hydroxypropyl and 3-hydroxypropyl).
As used herein, an example of xe2x80x9cC1-4 alkoxy-C1-4 alkylxe2x80x9d is methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, and the like.
As used herein, the term xe2x80x9chalo-substituted alkylxe2x80x9d refers to an alkyl radical as described above substituted with one or more halogens included, but not limited to, chloromethyl, dichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trichloroethyl, and the like.
As used herein, an example of xe2x80x9chalo-substituted alkoxyxe2x80x9d is chloromethoxy, dichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trichloroethoxy, and the like.
As used herein, the term xe2x80x9cC3-7 cycloalkylxe2x80x9d means carbocyclic radicals, of 3 to 7 carbon atoms, including, but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like.
As used herein, an example of xe2x80x9carylxe2x80x9d is phenyl and naphthyl.
As used herein, a 5-membered monocyclic aromatic group usually has one heteroatom selected from O, S and N in the ring. In addition to said heteroatom, the monocyclic aromatic group may optionally have up to three N atoms in the ring. For example, the 5-membered monocyclic aromatic group includes thienyl, furyl, thiazolyl (e.g., 1,3-thiazolyl, 1,2-thiazolyl), imidazolyl, pyrrolyl, oxazolyl (e.g., 1,3-oxazolyl, 1,2-oxazolyl, isoxazolyl), pyrazolyl, tetrazolyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl), oxadiazolyl (e.g., 1,2.3-oxadiazolyl), thiadiazolyl (e.g., 1,3,4-thiadiazolyl, 1,2,3-thiadiazolyl) and the like.
As used herein, an example of a 6-membered monocyclic aromatic group includes pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl (e.g., 1,3,5-triazinyl), tetrazinyl and the like.
As used herein, an example of a benzo-fuzed heterocycle includes quinolyl, isoquinolyl, cinnolinyl, quinoxalinyl, benzoimidazolyl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophenyl, indolyl, isoindolyl, 1H-indazolyl, quinazolinyl, phthalazinyl and the like.
As used herein, an example of (ethyl)(ethoxy)pyridyl includes 3-ethoxy-4-ethyl-2-pyridyl, 4-ethoxy-3-ethyl-2-pyridyl and the like.
As used herein, an example of (chloro)(ethyl)pyridyl includes 3-chloro-4-ethyl-2-pyridyl, 4-chloro-3-ethyl-2-pyridyl and the like.
As used herein, an example of (fluoro)(ethyl)phenyl includes 3-fluoro-4-ethyl-2-pyridyl, 4-fluoro-3-ethyl-2-pyridyl and the like.
Preferred compounds of this invention are those of the formula (I) wherein
Z is OH, C1-6 alkoxy, dimethylamino, methylamino, amino, N-methoxy-N-methylamino, 2-cyanoethylamino, 2-hydroxyethylamino, pyrrolidinyl, piperidino, piperazinyl, N-methyl-piperazinyl, morpholino, methoxyamino, piperazynyl, aminopyrrolidinyl or aminoethylamino.
Further preferred compounds of this invention are those of the formula (I) wherein
Z is OH or C1-6 alkoxy; and
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and the said cycloalkyl being optionally substituted with one substituent selected from OH, methyl, ethyl, propyl, F, Cl and CF3; and
(e) a benzo-fuzed heterocycle selected from quinolyl, isoquinolyl, cinnolinyl, quinoxalinyl, benzoimidazolyl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophenyl and indolyl, and the benzo-fuzed heterocycle being optionally substituted with one, two, or three substituents independently selected from the group (a-1).
Further preferred compounds of this invention are those of the formula (I) wherein
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) cyclopropyl, cyclobutyl and cyclohexyl; and
(e) quinolyl or isoquinolyl, and said quinolyl or isoquinolyl being optionally substituted with one substituent selected from the group halo, C1-4 alkyl, NH2, OH, C1-4 alkoxy and C1-4 halo-substituted alkyl.
Further preferred compounds of this invention are those of the formula (I) wherein
Z is OH, C1-6 alkoxy;
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); and
(e) isoquinolyl;
R1 is hydrogen or C1-4 alkyl;
R2 and R3 are independently H or methyl;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOR4, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, or 3.
Further preferred compounds of this invention are those of the formula (I) wherein
Z is OH, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy or tert-butoxy;
Q is selected from the following:
(a) phenyl optionally substituted with one or two substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, xe2x80x94COOH, C1-4 alkylsulfonylamino, nitro, C1-4 alkylsulfonyl and cyano,
(a-2) phenyl or benzyloxy, and the phenyl or phenyl moiety of benzyloxy being optionally substituted with one substituent selected from C1-4 alkyl, halo-substituted C1-4 alkyl, halo, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy and NH2,
(a-3) 5-membered monocyclic aromatic group selected from imidazolyl, thiazolyl, furyl, thienyl, pyrrolyl, tetrazolyl, triazolyl, oxazolyl, isoxazolyl, thiadiazolyl and pyrazolyl, and the 5-membered monocyclic aromatic group optionally being substitued with one substituent selected from C1-4 alkyl, halo-substituted C1-4 alkyl, halo, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy and NH2,
(a-4) 6-membered monocyclic aromatic group selected from pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl, and the 6-membered monocyclic aromatic group optionally being substitued with one substituent selected from C1-4 alkyl, halo-substituted C1-4 alkyl, halo, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy and NH2,
(b) a 6-membered monocyclic aromatic group selected from pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl, and said monocyclic armomatic group being optionally substituted with one or two substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group selected from imidazolyl, thiazolyl, furyl, thienyl, pyrrolyl, tetrazolyl, triazolyl, oxazolyl, isoxazolyl, thiadiazolyl and pyrazolyl, and said monocyclic aromatic group being optionally substituted with one or two substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
R1 is hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl or tert-butyl;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl and aminosulfonyl; and
n is 0, 1, 2, or 3.
Further preferred compounds of this invention are those of the formula (I) wherein
Z is OH, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxyor or tert-butoxy;
Q is selected from the following:
(a) phenyl optionally substituted with one or two substituents independently selected from
(a-1) fluoro, chloro, bromo, iodo, methyl, ethyl, propyl, butyl, CH2F, CHF2, CF3, methoxy, ethoxy, n-propoxy, n-butoxy, isopropoxy, CH2Fxe2x80x94Oxe2x80x94, CHF2xe2x80x94Oxe2x80x94, CF3xe2x80x94Oxe2x80x94, methylthio, ethylthio, hydroxymethyl, methoxymethyl, methoxyethyl, ethoxymethyl, hydroxy, nitro, methylsulfonyl, cyano, (HO)(H3C)2Cxe2x80x94, acetyl and methylsulfonylamino,
(a-2) phenyl or benzyloxy, and the phenyl or phenyl moiety of benzyloxy being optionally substituted with one substituent selected from methyl, ethyl, propyl, CF3, F, Cl, OH, methoxy, ethoxy and NH2,
(a-3) 5-membered monocyclic aromatic group selected from furyl, thienyl and pyrrolyl, and the 5-membered monocyclic aromatic group optionally being substitued with one substituent selected from methyl, ethyl, propyl, CF3, F, Cl, OH, methoxy, ethoxy and NH2,
(a-4) pyridyl optionally substitued with one substituent selected from methyl, ethyl, propyl, CF3, F, Cl, OH, methoxy, ethoxy and NH2,
(b) pyridyl optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-1), (a-2), (a-3) and (a-4),
(c) imidazolyl, thiazolyl, furyl, thienyl, isoxazolyl, 1,2,3-thiadiazolyl or pyrrolyl, and said imidazolyl, thiazolyl, furyl, thienyl, isoxazolyl, 1,2,3-thiadiazolyl or pyrrolyl being optionally substituted with one or two substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
R1 is hydrogen, methyl, ethyl, n-propyl, iso-propyl;
X is independently selected from fluoro, chloro, bromo, methyl, ethyl, propyl, butyl, CH2F, CHF2, CF3, methoxy, CF3O or ethoxy; and
n is 0, 1 or 2.
Further preferred compounds of this invention are those of the formula (I) wherein
Z is OH, ethoxy or methoxy; Q is phenyl, chlorophenyl, fluorophenyl, bromophenyl, methylphenyl, methoxyphenyl, (furyl)phenyl, trifluoromethylphenyl, trifluoromethoxyphenyl, pyridyl, methylpyridyl, ethylpyridyl, propylpyridyl, dimethlylpyridyl, chloropyridyl, fluoropyridyl, trifluoromethylpyridyl, methoxypyridyl, (ethyl)(ethoxy)pyridyl, (chloro)(ethyl)pyridyl, thiazolyl, methylthiazolyl, furyl, methoxymethylfuryl, isoquinolyl, cyclohexyl, methoxyphenyl, (fluoro)(ethyl)pyridyl, dimethylpyridyl or (ethoxy)(ethyl)pyridyl;
R1 is hydrogen; X is fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, CF3 or methoxy; and n is 1 or 2.
Further preferred compounds of this invention are those of the formula (I) wherein
Z is OH, ethoxy or methoxy; Q is phenyl, chlorophenyl, pyridyl, methylpyridyl, ethylpyridyl, propylpyridyl or chloropyridyl; R1 is hydrogen; X is fluoro, chloro, methyl or CF3; and n is 1 or 2.
Preferred individual compounds of this invention are:
ethyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid, sodium salt;
[6-chloro-2-(2-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(3-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[2-(4-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3,4-dichlorobenzoyl)-1H-indol-3-yl]acetic acid;
(2-benzoyl-4-chloro-1H-indol-3-yl)acetic acid;
[5-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[2-(3-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[5-methoxy-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
(2-benzoyl-7-chloro-1H-indol-3-y)acetic acid;
(2-benzoyl-4,5-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-4,6-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
dl-2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
less polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
more polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
(2-benzoyl-6-chloro-1H-indol-3-yl)-N,N-dimethylacetamide;
(2-benzoyl-6-chloro-1H-indol-3-yl)-N-methylacetamide;
(2-benzoyl-6-chloro-1H-indol-3-yl)acetamide;
(2-benzoyl-6-chloro-1H-indol-3-yl)-N-methoxy-N-methylacetamide;
2-(2-benzoyl-6-chloro-1H-indol-3-yl)-1-piperidino-1-ethanone;
2-(2-benzoyl-6-chloro-1H-indol-3-yl)-1-(4-methyl-1-piperazinyl)-1-ethanone;
(2-benzoyl-6-chloro-1H-indol-3-yl)-N-(2-cyanoethyl)acetamide;
(2-benzoyl-6-chloro-1H-indol-3-yl)-N-(2-hydroxyethyl)acetamide;
2-(2-benzoyl-6-chloro-1H-indol-3-yl)-1-morpholino-1-ethanone;
[2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-furylcarbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(cyclohexanecarbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethyl pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-tert-butylpyridine-2-carbonyl)-6-chloro-1H-indol-3-yl]acetate;
[2-(4-tert-butylpyridine-2-carbonyl)-6-chloro-1H-indol-3-yl]acetic acid;
methyl[2-(4-tert-butylpyridine-2-carbonyl)-5-chloro-1H-indol-3-yl]acetate;
[2-(4-tert-butylpyridine-2-carbonyl)-5-chloro-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(pyridine-3-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(pyridine-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(pyridine-4-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(pyridine-4-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(3,4-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(3,4-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-ethoxy-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-ethyl-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-ethyl-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetate;
[2-(4-methyl-2-pyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
methyl[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetate;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
methyl[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-methyl-2-(4-methyl pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl(2-benzoyl-1H-indol-3-yl)acetate;
(2-benzoyl-1H-indol-3-yl)acetic acid;
methyl[2-(4-chlorobenzoyl)-6-methyl-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-6-methyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-methyl-1H-indol-3-yl]acetic acid;
methyl[6-methoxy-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-methoxy-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-ethyl-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-ethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-isopropyl-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-isopropyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-trifluoromethoxy-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(2-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(2-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-benzyloxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-benzyloxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-hydroxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-hydroxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-benzoxybenzyloyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-benzyloxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-hydroxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-hydroxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-isopropoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-isopropoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-phenylbenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-phenylbenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-nitrobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-nitrobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[(4-methylsulfonyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[(4-methylsulfonyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(methylsulfonylamino)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(methylsulfonylamino)benzoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2,4-dichlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloro-3-fluorobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloro-3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-cyanobenzoyl)-1H-indol-3-yl]acetate;
methyl[6-chloro-2-[4-bromobenzoyl]-1H-indol-3-yl]acetate;
methyl[6-chloro-2-[4-(2-thienyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(2-thienyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(3-pyridyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(3-pyridyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(2-thiazolyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(2-thiazolyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-bromobenzoyl)-1H-indol-3-yl]acetate;
methyl[6-chloro-2-[3-(2-furyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[3-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl dl-2-[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]propionate;
dl-2-[2-(4-chlorobenzoyl)-6-chloro-1H-indol-3-yl]propionic acid;
methyl[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(isoquinolne-3-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-thienyl)carbonylindol-3-yl]acetic acid;
methyl[6-chloro-2-[3-(1-hydroxy-1-methylethyl)-2-furoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[3-(1-hydroxy-1-methylethyl)-2-furoyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetate;
methyl[5-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(imidazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(imidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(imidazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(imidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(1-methylpyrrole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(1-methylpyrrole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(thiazole-5-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(thiazole-5-carbonyl)-1H-indol-3-yl]acetic acid;
methyl(6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-[3-(ethoxypropyl)isoxazole-5-carbonyl]-1H-indol-3-yl]acetate;
[5-chloro-2-[3-(carboxy)isoxazole-5-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-cyclopropanecarbonyl-1H-indol-3-yl]acetate;
[6-chloro-2-cyclopropanecarbonyl-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-cyclobutanecarbonyl-1H-indol-3-yl]acetate;
[6-chloro-2-cyclobutanecarbonyl-1H-indol-3-yl)acetic acid;
methyl[5-(tert-butyl)-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[5-(tert-butyl)-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]-N,N-dimethylacetamide;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]-N-methylacetamide;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]-N-(2-hydroxyethyl)acetamide;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]-N-methoxyacetamide;
2-[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]-1-piperazinyl-1-ethanone;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]-N-(2-aminoethyl)acetamide;
2-[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]-1-(3-amino-1-pyrrolidinyl)-1-ethanone;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
methyl[6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-nitrobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2,4-dimethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-difuluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2,5-dimethoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-acetyl-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[5-acetyl-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetate;
methyl[6-fluoro-2-(4-methylpyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-fluoro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-fluoro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-5-methylthio-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-5-methylthio-1H-indol-3-yl]acetic acid, and a salt thereof.
Preferred individual compounds of this invention are:
ethyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid, sodium salt;
[6-chloro-2-(2-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(3-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[2-(4-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3,4-dichlorobenzoyl)-1H-indol-3-yl]acetic acid;
(2-benzoyl-4-chloro-1H-indol-3-yl)acetic acid;
[5-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chloro benzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[2-(3-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[5-methoxy-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
(2-benzoyl-7-chloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-4,5-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-4,6-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
dl-2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
less polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
more polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3yl]acetate;
[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
[2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-methylcarbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(cyclohexanecarbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-tert-butylpyridine-2-carbonyl)-6-chloro-1H-indol-3-yl]acetic acid;
[2-(4-tert-butylpyridine-2-carbonyl)-5-chloro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-4-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3,4-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-ethoxy-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chloro-4-ethyl pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-ethyl-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methyl-2-pyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
(2-benzoyl-1H-indol-3-yl)acetic acid;
[2-(4-chlorobenzoyl)-6-methyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-methyl-1H-indol-3-yl]acetic acid;
[6-methoxy-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-ethyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-isopropyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-benzyloxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-hydroxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-benzyloxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-hydroxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-isopropoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-phenylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-nitrobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[(4-methylsulfonyl)benzoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(methylsulfonylamino)benzoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2,4-dichlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chloro-3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-cyanobenzoyl)-1H-indol-3-yl]acetate;
methyl[6-chloro-2-[4-bromobenzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(2-thienyl)benzoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(3-pyridyl)benzoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(2-thiazolyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-bromobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-[3-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
dl-2-[2-(4-chlorobenzoyl)-6-chloro-1H-indol-3-yl]propionic acid;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-thienyl)carbonylindol-3-yl]acetic acid;
[6-chloro-2-[3-(1-hydroxy-1-methylethyl)-2-furoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(imidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(imidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(1-methylpyrrole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(thiazole-5-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-[3-(carboxy)isoxazole-5-carbonyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-cyclopropanecarbonyl-1H-indol-3-yl]acetic acid;
[6-chloro-2-cyclobutanecarbonyl-1H-indol-3-yl]acetic acid;
[5-(tert-butyl)-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoro-pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2-nitrobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2,4-dimethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-difuluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(2,5-dimethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-acetyl-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid, and a salt thereof.
Preferred individual compounds of this invention are:
ethyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(3-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[2-(4-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
(2-benzoyl-4-chloro-1H-indol-3-yl)acetic acid;
[5-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[2-(3-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
(2-benzoyl-4,5-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-4,6-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
dl-2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
less polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
more polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(6-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
[6-chloro-2-(2-furylcarbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(cyclohexanecarbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-tert-butylpyridine-2-carbonyl)-6-chloro-1H-indol-3-yl]acetate;
[2-(4-tert-butylpyridine-2-carbonyl)-6-chloro-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-ethoxy-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5,6-dichloro-2-(4-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-ethyl-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-ethyl-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-methyl-2-pyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-6-methyl-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-6-methyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-methyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-trifluoromethoxy-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetate, and a salt thereof.
Preferred individual compounds of this invention are:
ethyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(3-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[2-(4-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
(2-benzoyl-4-chloro-1H-indol-3-yl)acetic acid;
[5-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[2-(3-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
(2-benzoyl-4,5-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-4,6-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
dl-2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
less polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
more polar antipode, 2-(2-benzoyl-6-chloro-1H-indol-3-yl)propanoic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
[6-chloro-2-(2-furylcarbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(cyclohexanecarbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-tert-butylpyridine-2-carbonyl)-6-chloro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-ethoxy-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-methoxy-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-ethyl-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methyl-2-pyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-6-methyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-methyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylisoxazole-3-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(1-methylimidazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
2-{6-chloro-2-[(4-ethyl-3-fluoro-2-pyridinyl)carbonyl]-1H-indol-3-yl}acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetate, and a salt thereof.
Preferred individual compounds of this invention are:
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(4-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(3-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[2-(4-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[2-(3-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
(2-benzoyl-4,5-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-4,6-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
[6-chloro-2-(cyclohexanecarbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl)acetate;
[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-y ]acetic acid;
methyl[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-ethoxy-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetate;
[2-(4-methyl-2-pyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
methyl[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]a acetate;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-methyl-1H-indol-3-yl]acetic acid;
methyl[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-chlorobenzoyl)-5-trifluoromethy-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetate, and a salt thereof.
Preferred individual compounds of this invention are:
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(4-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-fluorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(3-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[2-(4-bromobenzoyl)-6-chloro-1H-indol-3-yl]acetic acid;
[62-chloro-2-(4-trifluoromethylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-methylbenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[2-(3-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
(2-benzoyl-4,5-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-4,6-dichloro-1H-indol-3-yl)acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(thiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl(2-benzoyl-6-chloro-1H-indol-3-yl)acetate;
[6-chloro-2-(cyclohexanecarbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(6-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-ethoxy-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-ethyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-isopropyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-1H-indol-3-yl]acetic acid;
[5-tert-butyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methyl-2-pyridine-2-carbonyl)-5-trifluoromethoxy-1H-indol-3-yl]acetic acid;
[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-trifluoromethoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(2-furyl)benzoyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[3-methoxymethyl-2-furoyl]-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(2-methylimidazole-4-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methylthiazole-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl]-1H-indol-3-yl)acetic acid;
methyl[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetate;
[6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid, and a salt thereof.
Preferred individual compounds of this invention are:
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetate;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetatic acid;
methyl[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetate;
[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate;
[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
methyl[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetate;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid (cj-020,099);
methyl[6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetate, and a salt thereof.
Most preferred individual compounds are:
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid, and a salt thereof.
Preferred pharmaceutical compositions of this invention comprise those compounds of the formula (I), wherein the compound is as defined above.
Most preferred individual compounds to be contained in the pharmaceutical compositions are:
(2-benzoyl-6-chloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(3-chlorobenzoyl)-1H-indol-3-yl]acetic acid;
[2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid;
(2-benzoyl-5,6-dichloro-1H-indol-3-yl)acetic acid;
[6-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-isopropylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-propylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-methyl-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-1-indol-3-yl]acetic acid;
[6-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-methoxypyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(4-methoxybenzoyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-[4-(1-hydroxyethyl)pyridine-2-carbonyl]-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(5-chloropyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[6-methyl-2-(4-methyl pyridine-2-carbonyl)-1H-indol-3-yl]acetic acid;
[5-chloro-2-(isoquinoline-3-carbonyl)-1H-indol-3-yl]acetic acid;
[6-chloro-2-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid, and a salt thereof.
Also, the present invention provides a process for prepraing a compound of the formula: 
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises the steps of:
i) reacting a compound of the formula: 
wherein B is a suitable protecting group; R5 is C1-6 alkyl; X and n are as defined above, with a compound of the formula: 
wherein E is halo and Q are as defined above, with a first base and a suitable solvent;
ii) reacting the product of step i) with a second base.
iii) reacting the product of step ii) with an acid.
Prefered process of the above mentioned process is a process, wherein said first base is potassium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate or cesium carbonate.
Prefered process of the above mentioned process is a process, wherein said first base is potassium carbonate.
Prefered process of the above mentioned process is a process, wherein said second base is aqueous sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium pentoxide (followed by water), sodium methoxide (followed by water) or potassium t-butoxide (followed by water).
Prefered process of the above mentioned process is a process, wherein said second base is sodium hydroxide.
Prefered process of the above mentioned process is a process, wherein said acid is aqueous hydrochloric acid, hydrobromic acid, sulfuric acid or ammonium chloride.
Prefered process of the above mentioned process is a process, wherein said acid is aqueous hydrochloric acid.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone, or tetrahydrofuran.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylaetamide.
Also, the present invention provides a process for prepraing a compound of the formula: 
wherein
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises reacting a compound of the formula: 
wherein R5 is C1-6 alkyl; Q, X and n are as defined as before, with a base in a suitable solvent.
Prefered process of the above mentioned process is a process, wherein said base is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium t-pentoxide, sodium methoxide, sodium ethoxide or potassium t-butoxide.
Prefered process of the above mentioned process is a process, wherein said base is sodium hydroxide.
Prefered process of the above mentioned process is a process, wherein said solvent is an aqueous mixture of methanol, ethanol, isopropyl alcohol or tetrahydrofuran.
Prefered process of the above mentioned process is a process, wherein said solvent is methanol containing water.
Also, the present invention provides a process for prepraing a compound of the formula: 
wherein
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; R5 is C1-6 alkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises reacting a compound of the formula: 
wherein B, Q, X, n and R5 are as defined above with a base in a suitable solvent.
Prefered process of the above mentioned process is a process, wherein said base is 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,1,3,3-tetramethylguanidine, sodium t-pentoxide, sodium methoxide, or potassium t-butoxide.
Prefered process of the above mentioned process is a process, wherein said base is 1,8-diazabicyclo[5.4.0]undec-7-ene or potassium t-butoxide.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone, or tetrahydrofuran.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylacetamide.
Also, the present invention provides a process for prepraing a compound of the formula: 
wherein B is a suitable protecting group;
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; R5 is C1-6 alkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises reacting a compound of the formula: 
wherein B, Q, X, n and R5 are as defined above, with a base in the presence of a solvent.
Prefered process of the above mentioned process is a process, wherein said base is potassium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate, or cesium carbonate.
Prefered process of the above mentioned process is a process, wherein said base is potassium carbonate.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone, or tetrahydrofuran.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylacetamide.
Also, the present invention provides a process for prepraing a compound of the formula: 
wherein B is a suitable protecting group;
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; R5 is C1-6 alkyl; and
n is 0, 1, 2, 3 or 4,
which comprises reacting a compound of the formula: 
wherein B, X, n and R5 are as defined above, with a compound of the formula: 
wherein E is halo and Q arc as defined above, with a base in the presence of a solvent.
Prefered process of the above mentioned process is a process, wherein said base is potassium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate, or cesium carbonate.
Prefered process of the above mentioned process is a process, wherein said base is potassium carbonate.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone or tetrahydrofuran.
Prefered process of the above mentioned process is a process, wherein said solvent is N,N-dimethylacetamide.
Also, the present invention provides a process for prepraing a compound of the formula: 
wherein
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R1 is hydrogen, C1-4 alkyl or halo;
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
R5 is C1-6 alkyl;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises treating a compound of the formula (X): 
wherein R1, R5, X, Q and n are as defined herein before, and B is a suitable protecting group, in the presence of a suitable base to obtain a compound of the formula (XII).
Also, the present invention provides a process for prepraing a compound of the formula: 
wherein
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R1 is hydrogen, C1-4 alkyl or halo;
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
R5 is C1-6 alkyl;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises reacting a compound of the formula (IX): 
wherein R1, R5, X, and n are as defined above, and B is a suitable protecting group, with a compound of the formula (XI): 
in the presence of a suitable base at a temperature of xe2x88x9240xc2x0 C. to 200xc2x0 C. to obtain a compound of the formula (XII).
Prefered process of the above mentioned process is a process, wherein the reaction is carried out at a temperature of 0xc2x0 C. to 100xc2x0 C.
Prefered process of the above mentioned process is a process, wherein the suitable base is potassium carbonate, cesium carbonate, sodium carbonate, sodium tert-butoxide, potassium tert-butoxide, sodium hydride, potassium hydride or potassium fluoride.
Prefered process of the above mentioned process is a process, wherein the reaction is firstly carried out in the presence of a base for 2 minutes to a day; and then, another base is added to the reaction mixture.
Prefered process of the above mentioned process is a process, wherein the reaction is firstly carried out for 30 minutes to 8 hours.
Prefered process of the above mentioned process is a process, wherein the suitable protecting group is methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, phenylsulfonyl, p-toluenesulfonyl, methanesulfonyl or trifluoromethanesulfonyl.
Prefered process of the above mentioned process is a process, wherein the suitable protecting group is phenylsulfonyl, p-toluenesulfonyl, methanesulfonyl or trifluoromethanesulfonyl.
Prefered process of the above mentioned process is a process, wherein the first base is selected from sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, cesium carbonate, potassium fluoride, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, pyridine, pyrrolidine, triethylamine, diisopropylamine, diisopropylethylamine and diethylisopropylamine; and the second base is selected from sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, cesium carbonate, potassium fluoride, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, pyridine, pyrrolidine, triethylamine, diisopropylamine, diisopropylethylamine and diethylisopropylamine.
Prefered process of the above mentioned process is a process, wherein the first base is selected from potassium carbonate, cesium carbonate, sodium hydride and potassium fluoride; and the second base is selected from 1,8-diazabicyclo[5.4.0]undec-7-ene, cesium carbonate, pyrrolidine, diisopropylamine, triethylamine, diethylisopropylamine and diisopropylethylamine.
Prefered process of the above mentioned process is a process, wherein the first base is potassium carbonate, cesium carbonate or potassium fluoride; and the second base is 1,8-diazabicyclo[5.4.0]undec-7-ene, potassium tert-butoxide or cesium carbonate.
Prefered process of the above mentioned process is a process, wherein the combination of the first base and the second base (first base/second base) is selected from potassium carbonate/1,8-diazabicyclo[5.4.0]undec-7-ene, potassium carbonate/cesium carbonate, cesium carbonate/potassium tert-butoxide, cesium carbonate/1,8-diazabicyclo[5.4.0]undec-7-ene and potassium fluoride/1,8-diazabicyclo[5.4.0]undec-7-ene and potassium fluoride/cesium carbonate.
Prefered process of the above mentioned process is a process, wherein the combination of the first base and the second base (first base/second basse) is selected from potassium carbonate/1,8-diazabicyclo[5.4.0]undec-7-ene, potassium carbonate/cesium carbonate and cesium carbonate/potassium tert-butoxide.
Also, the present invention provides a process for prepraing a compound of the formula: 
wherein
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NO2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R1 is hydrogen, C1-4 alkyl or halo;
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises treating a compound of the formula (X): 
wherein R1, R5, X, Q and n are as defined here before, with a suitable base under hydrolyzing conditions to obtain the compound of formula (VIII).
This invention also provides a process for preparing a compound of the formula (VIII): 
wherein
Q is selected from the following:
(a) phenyl optionally substituted with one, two or three substituents independently selected from
(a-1) halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2R3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl,
(a-2) aryl or xe2x80x94Oxe2x80x94(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino and CN,
(b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4),
(c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4);
(d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, C1-4 alkyl, halo and halo-substituted C1-4 alkyl; and
(e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1);
R1 is hydrogen, C1-4 alkyl or halo;
R2 and R3 are independently H, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy, NH2 or CN;
X is independently selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino, C1-4 alkylamino, CN, HOxe2x80x94(C1-4)alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, xe2x80x94NH2S(O)2NR2NR3, acetyl, xe2x80x94COOH, xe2x80x94C(O)Oxe2x80x94C1-4 alkyl, C1-4 alkylsulfonylamino and C3-7 cycloalkyl; and
n is 0, 1, 2, 3 or 4,
which process comprises hydrolyzing a compound of the formula (XII): 
wherein R5 is C1-6 alkyl, R1, X, Q and n are as defined herein before.
A compound of general formula (I) may be prepared by any synthetic procedure applicable to structure-related compounds known to those skilled in the art. The following representative examples as described hereinafter are illustrative and are not meant to limit the scope of the invention in anyway. Unless otherwise stated, Q, X, Z, R1, and n are as defined above. 
Scheme 1:
In one embodiment, for example, a compound of the formula (VI) may be prepared according to the reaction sequences depicted in Scheme 1. (Compound (VI) corresponds to a compound (I) wherein R1 is H, and Z is OH.) 
In brief, a compound of formula (III) is subjected to oxidative homolytic malonylation (for leading references see J. M. Muchowski et al; Can. J. Chem., 70, 1838, 1992 and E. Baciocchi et al; J. Org. Chem., 58, 7610, 1993). In one example, a compound of the formula (III) is reacted with a suitable malonyl radical generated from a compound of formula C(R4)H(CO2R5)2, wherein R4 is hydrogen or halogen, preferably chloro, and R5 is C1-6 alkyl, and a manganese(III) agent, preferably manganese(III) triacetate. The manganese(III) agent is usually used in stoichiometric amounts but, alternatively, may be made catalytic by use of a suitable reoxidizing agent such as sodium persulfate, usually in the presence of a co-catalyst such as, a silver(I) salt such as silver nitrate. A preferred reaction solvent is acetic acid; however, acetic acid-acetic anhydride or other protic solvents such as propionic acid can be used. The reaction is preferably conducted in the presence of sodium acetate or potassium acetate, but, may be conducted in solvent alone. Reaction temperatures are generally in the range of room temperature (e.g., 25xc2x0 C.) to reflux temperature of solvent, preferably 60 to 100xc2x0 C., but if necessary, lower or higher temperature can be employed. Reaction times are, in general, from one hour to a day, preferably from 4 to 16 hours, however shorter or longer reaction times, if necessary, can be employed. In the immediate instance, the xcex1-acetoxy compounds of formula (IV) is usually obtained as the major product. Compounds of formula (IV) can readily be transformed to compounds of formula (V) by reduction with a suitable reducing agent, for example, a trialkylsilane, sodium xcex1-(dimethylamino)naphtalenide, lithium in liquid ammonia, sodium naphtalenide, preferably triethylsilane in a suitable protic solvent, notably, trifluoroacetic acid. Alternatively, the reaction can be conducted in a reaction inert co-solvent such as dichloromethane or 1,2-dichloroethane. Reaction temperatures are generally in the range of room temperature to reflux temperature of solvent, preferably 15 to 100xc2x0 C., but if necessary, lower or higher temperature can be employed. Reaction times are, in general, from several minutes to a day, preferably from 20 minutes to 5 hours, however shorter or longer reaction times, if necessary, can be employed. Alternatively, a compound of formula (V) may be obtained directly from a compound of formula (III) from a malonyl radical generated from (i) a suitable monohalomalonate, preferably, bromomalonate, mediated by aerial oxidation of a trialkylborane such as triethylborane (see B. Giese; In Radicals in organic synthesis: formation of carbon-carbon bonds. Pergamon Press, Oxford. pp. 86-89, 1986, and P. G. Allies and P. B. Brindley; J. Chem. Soc. (B), 1126, 1960) or, (ii) a malonic ester in the presence of a cerium(IV) salt such as cerium(IV) ammonium nitrate (for example, see E. Baciocchi et al; Tetrahedron Lett, 2763, 1986). A compound of formula (V) may be readily transformed to a compound of formula (VI) by subjection to standard saponification/decarboxylation conditions.
Scheme 2:
Alternatively, as depicted in Scheme 2, a compound of the formula (VIII) (a compound (I) wherein Z is OH), wherein R1 is C1-4 alkyl, may be prepared in an analogous manner to that of a compound of formula (VI) employing appropriate reaction conditions as described by illustration herein above from a suitable monoalkylmalonate, wherein R1 is C1-4 alkyl, W is hydrogen or a halogen, preferably bromide, and R5 is C1-6 alkyl, from a compound of formula (III). 
In Scheme 2, for example, the oxidant is manganese(III) agent such as manganese(III) triacetate, or Cerium(IV) agent such as ammonium Cerium(IV) nitrate and Cerium(IV) sulfate.
Scheme 3:
In another embodiment, a compound of formula (VIII) is readily accessible from the appropriate 2-aminocinnamic acid ester (IX) wherein B is a suitable protecting group, for example, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl (Boc), benzyloxycarbonyl, phenylsulfonyl, p-toluenesulfonyl, methanesulfonyl, trifluoromethanesulfonyl, methanesulfonyl or trifluoromethanesulfonyl (preferably phenylsulfonyl, p-toluenesulfonyl, methanesulfonyl or trifluoromethanesulfonyl). 
In Scheme 3, the requisite 2-aminocinnamic acid ester (IX) is reacted with a compound of formula (XI), wherein Q is as defined above and E is halogen, preferably, iodo, bromo or chloro, in the presence of a suitable base. A suitable base is, for example, an alkali or alkaline earth metal alkoxide, carbonate, fluoride or hydride, such as sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium fluoride or potassium hydride. Preferred reaction inert solvents include, but are not limited to, acetone, methyl ethyl ketone, acetonitrile, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), dimethylsulfoxide (DMSO), dioxane or tetrahydrofuran (THF). Reaction temperatures are preferably in the range of xe2x88x9240xc2x0 C. to reflux temperature of solvent (for example 200xc2x0 C.), usually in the range of 0xc2x0 C. to 100xc2x0 C., but if necessary, lower or higher temperature can be employed. Reaction time is in general from 2 minutes to a day, preferably from 30 minutes to 8 hours, however shorter or longer reaction times, if necessary, can be employed. When the reaction is, for example, conducted at room temperature (e.g., 25xc2x0 C.) the intermediate indoline (X) can be isolated. Reaction at higher temperatures (e.g., 40 to 100xc2x0 C.) can result in formation of indole (XII). Usually the intermediate indoline (X) is not isolated but either (i) hydrolyzed with commitant formation of the indole ring directly to a compound of formula (VIII) under standard conditions known to those skilled in the art, or (ii) transformed to a compound of formula (XII) by using a suitable base, for example, an alkali or alkaline earth metal carbonate such as sodium carbonate, potassium carbonate or cesium carbonate, or an organic base such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), pyridine, pyrrolidine, triethylamine, diisopropylamine, diisopropylethylamine, diethylisopropylamine, Hunig""s base, potassium tert-butoxide, sodium tert-butoxide, or the like, or a suitable oxidant such as cerium(IV) ammonium nitrate (CAN), manganese(IV) oxide, manganese(III) triacetate, copper(II) acetate/air, chloranil, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), N-methylmorpholine-N-oxide, or the like (for example, see H. Dumoulin et al; J. Heterocycl. Chem., 32, 1703, 1995; H. Rapoport et al; Tetrahedron Lett., 5053, 1991; P. Martin et al; Helv. Chim. Acta, 77, 111, 1994; Y. Kikugawa et al, J. Chem. Soc. Perkins Trans 1, 7, 1401, 1984; A. Goti et al; Tetrahedron Lett., 6567, 1996; L. S. Liebeskind et al; J. Org. Chem, 61, 2594, 1996). Preferred reaction inert solvents include, but are not limited to, acetone, methyl ethyl ketone, acetonitrile, dioxane or tetrahydrofuran (THF). Reaction temperatures are preferably in the range of 0xc2x0 C. to reflux temperature of solvent, usually in the range of 15 to 60xc2x0 C., but if necessary, lower or higher temperature can be employed. Reaction time is in general from several minutes to a day, preferably from 30 minutes to 8 hours, however shorter or longer reaction times, if necessary, can be employed. A compound of formula (XII) may be readily hydrolyzed to a compound of formula (VIII) under standard conditions.
Scheme 4:
In another embodiment, a compound of formula (VIII), wherein Q, X, R1 and n are as defined above, may be prepared as illustrated in Scheme 4. 
For example, treatment of a compound of formula (XIII), wherein R1, R5, X and n are as defined above, with a trialkyltin hydride, e.g., tributyltin hydride usually in the presence of a radical initiator such as, 2,2xe2x80x2-azabisisobutyronitrile (AIBN), affords the intermediate 2-stannylindole (XIV) via an intramolecular radical cyclization as described in J. Am. Chem. Soc., 116, 3127, (1994); T. Fukuyama et al. The intermediate (XIV) generated in situ is subsequently treated with an acyl halide, wherein Q and E are as defined above, in the presence of a suitable palladium catalyst according to Stille""s procedure (for example see. J. K. Stille et al; J. Am. Chem. Soc., 109, 813, 5478, (1987) and J. Am. Chem. Soc., 106, 4833, (1984)) to afford indole (XII) which may be hydrolyzed to a compound of formula (VIII) by conventional procedure.
Examples of the palladium catalyst are
tetrakis(triphenylphosphine)palladium(0),
dichlorobis(triphenylphosphine)palladium(II),
bis(dibenzylideneacetone)palladium(0),
benzyl(chloro)bis(triphenylphosphine)palladium(II),
bis(acetonitrile)dichloropalladium(II).
Scheme 5:
In another embodiment, a compound of formula (VIII), wherein Q, X, R1 and n are as defined above, may be prepared as illustrated in Scheme 5. 
For example, treatment of a compound (XV), wherein R1, X and n are as defined above, is reacted with a compound of formula Qxe2x80x94C(O)xe2x80x94A affords a compound of formula (VIII), or a compound of formula (XVI) (for example see U. Pindur et al., Liebigs Ann. Chem., 601 (1991) and C. J. Moody et al., J. Chem. Soc. Perkin Trans. I, 3249 (1988)) which may be hydrolyzed to a compound of formula (VIII) by conventional procedure (for example see E. B. Fray et al., Tetrahedron, 49, 439 (1993) and U. Pindur et al., J. Heterocycl. Chem., 29, 145 (1992)). In a compound of formula Axe2x80x94C(O)xe2x80x94Q, A is defined such that the compound of Axe2x80x94C(O)xe2x80x94Q is, for example, an acyl halide, carboxylic acid, carboxylic acid anhydride, a mixed carboxylic sulfonic anhydride, or the like. The reaction may be conducted in the presence or absence of catalyst, preferably in the presence of catalyst such as, boron trifluoride-diethyl ether, tin(IV) chloride, aluminum chloride, ferric chloride, zinc chloride, iodine, iron, or the like. Preferred reaction inert solvents include, but are not limited to, diethyl ether, dichloromethane, 1,2-dichloroethane, carbon disulfide, nitrobenzene or nitromethane. Reaction temperatures are preferably in the range of xe2x88x9278 to 210xc2x0 C., usually in the range of xe2x88x9210xc2x0 C. to reflux temperature of solvent, but if necessary, lower or higher temperature can be employed. Reaction time is in general from several minutes to a day, preferably from 30 minutes to 8 hours, however shorter or longer reaction times, if necessary, can be employed.
Scheme 6:
Acetic acid compounds of formulae (VI) and (VIII) as described in the aforementioned schemes may be readily transformed to the corresponding amide, compounds of formulae (XVII) and (XVIII), or ester, compound of formula (XII), by any conventional method known to those skilled in the art. 
As depicted in Scheme 6, compounds of formulae (XVII) and (XVIII) can be readily prepared by treating the requisite acetic acid compounds of formulae (VI) and (VIII) with an appropriate amine, wherein R2, R3, Y and r are as described herein before, in the presence of a suitable coupling reagent such as, but not limited to, 1-(dimethylaminopropyl)-3-ethylcarbodiimide (WSC), N,Nxe2x80x2-dicyclohexylcarbodiimidazole (DCC), carbonyldiimidazole, diethylphosphorocyanidate (DEPC), or the like. Preferred reaction inert solvents include, but are not limited to, acetone, acetonitrile, dichloromethane, 1,2-dichloroethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), dimethylsulfoxide (DMSO), dioxane, tetrahydrofuran (THF) or pyridine. Reaction temperatures are preferably in the range of 40 to 150xc2x0 C., usually in the range of 15xc2x0 C. to reflux temperature of solvent, but if necessary, lower or higher temperature can be employed. Reaction time is in general from several minutes to a day, preferably from 30 minutes to 8 hours, however shorter or longer reaction times, if necessary, can be employed. The compounds of formulae (VI) and (VIII) can also be readily transformed to the corresponding ester by conventional methods. 
(wherein B is a suitable protecting group, R5 is C1-6 alkyl, E is halo, Q, X and n is as defined above.)
In Scheme 7, the starting material of formula 7-I may be prepared according to methods familiar to those of ordinary skill in the art, including one or more synthetic procedures described in R. W. Carling, P. D. Leeson, K. Moore, J. D. Smith, C. R. Moyes, J. Med. Chem., 1993, pages 3397-3408.
The compound of formula 7-II is prepared from a compound of formula 7-I by treatment with a base and an electrophile in a suitable solvent. Suitable bases include such as triethylamine, diisopropylethylamine, or pyridine optionally substituted by 1 to 3 (C1-C4)alkyl groups, preferably pyridine. Suitable electrophiles include methanesulfonyl chloride or anhydride, or phenylsulfonyl chloride wherein the phenyl moiety of said phenylsulfonyl optionally includes 1 or 2 substituents selected from halo, nitro, and (C1-C4)alkyl. Suitable solvents include dichloromethane, dichloroethane, methyl t-butyl ether, disopropyl ether or toluene, preferably dichloromethane. The temperature of the aforesaid reaction may range from about 0xc2x0 C. to about 50xc2x0 C., preferably about room temperature (20-25xc2x0 C.) for a period of about 1 to 30 hours, preferably about 18 hours.
The compound of formula 7-IV is prepared from a compound of formula 7-II by treatment with a first base and an alkylating agent of the formula 7-III in the presence of a solvent followed by reaction with a second base followed by reaction with an acid. Suitable first bases include potassium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate or cesium carbonate, preferably potassium carbonate. Suitable solvents include N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone or tetrahydrofuran, preferably N,N-dimethylaetamide. The aforesaid reaction is performed at a temperature ranging from about 0xc2x0 C. to about 100xc2x0 C., preferably room temperature (20-25xc2x0 C.), for a period of time of about 10 minutes to 5 hours, typically 15 minutes. Suitable second bases include an aqueous solution of a base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium t-pentoxide (followed by water), sodium methoxide (followed by water) or potassium t-butoxide (followed by water), preferably sodium hydroxide. The reaction with the second base is performed at a temperature ranging from about 20xc2x0 C. to about 120xc2x0 C., preferably 100xc2x0 C., for a period of time of about 1 hour to 24 hours, typically 8 hours. Suitable acids include aqueous hydrochloric acid, hydrobromic acid, sulfuric acid or ammonium chloride, preferably hydrochloric acid. The reaction with the acid is performed at a temperature ranging from about 0xc2x0 C. to about 50xc2x0 C., preferably about 20xc2x0 C. to about 25xc2x0 C., for a period of time of about xc2xd hour to about 6 hours, typically about 1 hour.
Alternatively, the conversion of the compound of formula 7-II to a compound of formula 7-IV can be accomplished stepwise. The compound of formula 7-V may be prepared from a compound of formula 7-II by treatment with a base and an alkylating agent of formula 7-III in the presence of a solvent. Suitable bases include potassium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate, or cesium carbonate, preferably potassium carbonate. Suitable solvents include N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone or tetrahydrofuran, preferably N,N-dimethylacetamide. The temperature for the aforesaid reaction may range from about 0xc2x0 C. to about 50xc2x0 C., preferably room temperature (20-25xc2x0 C.), for a period of time of about 10 minutes to 40 minutes, typically 30 minutes.
The compound of formula 7-VI is prepared from a compound of formula 7-V by reaction with a base in the presence of a solvent. Suitable bases include potassium carbonate, potassium bicarbonate, sodium bicarbonate, sodium carbonate or cesium carbonate, preferably potassium carbonate. Suitable solvents include N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone or tetrahydrofuran, preferably N,N-dimethylacetamide. The temperature for the aforesaid reaction may range from about 0xc2x0 C. to about 50xc2x0 C., preferably room temperature (20-25xc2x0 C.), for a period of time of about 1 hour to 6 hours, preferably 4 hours.
The compound of formula 7-VII is prepared from a compound of formula 7-VI by reaction with a base in a suitable solvent. Suitable bases include 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,1,3,3-tetramethylguanidine, sodium t-pentoxide, sodium methoxide or potassium t-butoxide, preferably 1,8-diazabicyclo[5.4.0]undec-7-ene methoxide or potassium t-butoxide. Suitable solvents include N,N-dimethylacetamide, N,N-dimethylformamide, methyl ethyl ketone, acetone or tetrahydrofuran, preferably N,N-dimethylacetamide. The temperature for the aforesaid reaction may range from about 0xc2x0 C. to 100xc2x0 C., preferably room temperature (20-25xc2x0 C.), for a period of 30 minutes to 5 hours, preferably 1 hour.
The compound of formula 7-IV is prepared from a compound of formula 7-VII by treatment with a base in a suitable solvent. Suitable bases include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium t-pentoxide, sodium methoxide, sodium ethoxide or potassium t-butoxide, preferably sodium hydroxide. Suitable solvents include an aqueous mixture of methanol, ethanol, isopropyl alcohol or tetrahydrofuran, preferably methanol, containing water. The temperature of the aforesaid reaction may range from about 10xc2x0 C. to 100xc2x0 C., preferably room temperature (20-25xc2x0 C.), for a period of 12 to 48 hours, preferably 24 hours, to provide the carboxylate salt of compound of formula 7-IV which can then be treated with an acid to provide the compound of formula 7-IV.
The compound of formula 7-VI has asymmetric atoms and therefore exist in different enantiomeric and diastereomeric forms. Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods known to those skilled in the art, for example, by chromatography or fractional crystallization. The use of all such isomers, including diastereoisomer mixtures and pure enantiomers, are considered to be part of the present invention.
The starting materials in the aforementioned general syntheses may be obtained by conventional methods known to those skilled in the art. The preparation of such starting materials is described within the accompanying non-limiting examples which are provided for the purpose of illustration only. Alternatively, requisite starting materials may be obtained by analogous procedures, or modifications thereof, to those described hereinafter.
The products which are addressed in the aforementioned general syntheses and illustrated in the experimental examples described herein after may be isolated by standard methods and purification can be achieved by conventional means known to those skilled in the art, such as distillation, crystallization or chromatography techniques.
Certain compounds described herein contain one or more asymmetric centers and are capable of existing in various stereoisomeric forms. The present invention contemplates all such possible stereoisomers as well as their racemic and resolved, enantiomerically pure forms and pharmaceutically acceptable salts thereof Certain compounds of the present invention are capable of forming addition salts with inorganic or organic acids. The pharmaceutically acceptable acid salts of the compounds of formula (I) are those which form non-toxic addition salts, such as, but not limited to, the hydrochloride, hydrobromide, sulfate or bisulfate, acetate, benzoate, besylate, citrate, fumarate, glucuronate, hippurate, lactate, tartrate, saccharate, succinate, maleate, methanesulfonate, p-toluenesulfonate, phosphate and pamoate (i.e., 4,4xe2x80x2-methylene-bis-(3-hydroxy-2-naphthoate)) salts. The pharmaceutically acceptable acid salts may be prepared by conventional techniques.
Certain compounds of the present invention are capable of forming pharmaceutically acceptable non-toxic cations. Pharmaceutically acceptable non-toxic cations of compounds of formula (I) may be prepared by conventional techniques by, for example, contacting said compound with a stoichiometric amount of an appropriate alkali or alkaline earth metal (sodium, potassium, calcium and magnesium) hydroxide or alkoxide in water or an appropriate organic solvent such as ethanol, isopropanol, mixtures thereof, or the like.
Also included within the scope of this invention are bioprecursors (also called pro-drugs) of the compounds of the formula (I). A bioprecursor of a compound of the formula (I) is a chemical derivative thereof which is readily converted back into the parent compound of the formula (I) in biological systems. In particular, a bioprecursor of a compound of the formula (I) is converted back to the parent compound of the formula (I) after the bioprecursor has been administered to, and absorbed by, a mammalian subject, e.g., a human subject. When the compounds of the formula (I) of this invention may form solvates such as hydrates, such solvates are included within the scope of this invention.
An example of prodrug of the compound of formula (I) is a compound of the formula (I), wherein the 1st position of indole ring is substituted with a group selected from hydroxymethyl, xe2x80x94C(O)xe2x80x94C1-4 alkyl, xe2x80x94C(O)xe2x80x94(NH2)CHxe2x80x94(C1-4 alkyl), xe2x80x94C(O)-phenyl, xe2x80x94CH2NHC(O)-aryl, xe2x80x94CH2xe2x80x94C1-4 alkyl-Oxe2x80x94C(O)xe2x80x94C1-4 alkyl, xe2x80x94C1-4 alkyl-pyridyl, xe2x80x94C(O)CH2NR2 and xe2x80x94CH2N(C1-4 alkyl)2.
Another example of prodrug of the compound of formula (I) is a compound of the formula (I), wherein the carboxyl group is substituted with a group selected from C1-4 alkyl, xe2x80x94CH2xe2x80x94C1-4 alkyl-Oxe2x80x94C(O)xe2x80x94C1-4 alkyl, xe2x80x94CH2xe2x80x94C1-4alkyl-Oxe2x80x94C(O)xe2x80x94N(C1-4 alkyl)2, xe2x80x94CH2C(O)xe2x80x94N(C1-4 alkyl)2, xe2x80x94CH2xe2x80x94C1-4 alkyl-Oxe2x80x94C(O)xe2x80x94Oxe2x80x94C1-4alkyl, ethyl-OH and xe2x80x94CH2CO2H.
The compounds of the formula (I) of this invention can be administered via either the oral, parenteral or topical routes to mammals. In general, these compounds are most desirably administered to humans in doses ranging from 0.01 mg to 100 mg per kg of body weight per day, although variations will necessarily occur depending upon the weight, sex and condition of the subject being treated, the disease state being treated and the particular route of administration chosen. However, a dosage level that is in the range of from 0.01 mg to 10 mg per kg of body weight per day, single or divided dosage is most desirably employed in humans for the treatment of abovementioned diseases.
The compounds of the present invention may be administered alone or in combination with pharmaceutically acceptable carriers or diluents by either of the above routes previously indicated, and such administration can be carried out in single or multiple doses. More particularly, the novel therapeutic agents of the invention can be administered in a wide variety of different dosage forms, i.e., they may be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, trochees, hard candies, powders, sprays, creams, salves, suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups, and the like. Such carriers include solid diluents or fillers, sterile aqueous media and various nontoxic organic solvents, etc. Moreover, oral pharmaceutical compositions can be suitably sweetened and/or flavored. In general, the therapeutically-effective compounds of this invention are present in such dosage forms at concentration levels ranging 5% to 70% by weight, preferably 10% to 50% by weight.
For oral administration, tablets containing various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dipotassium phosphate and glycine may be employed along with various disintegrants such as starch and preferably corn, potato or tapioca starch, alginic acid and certain complex silicates, together with granulation binders like polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for tabletting purposes. Solid compositions of a similar type may also be employed as fillers in gelatine capsules; preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene grycols. When aqueous suspensions and/or elixirs are desired for oral administration, the active ingredient may be combined with various sweetening or flavoring agents, coloring matter or dyes, and, if so desired, emulsifying and/or suspending agents as well, together with such diluents as water, ethanol, propylene glycol, glycerin and various combinations thereof.
For parenteral administration, solutions of a compound of the present invention in either sesame or peanut oil or in aqueous propylene glycol may be employed. The aqueous solutions should be suitably buffered (preferably pH greater than 8) if necessary and the liquid diluent first rendered isotonic. These aqueous solutions are suitable for intravenous injection purposes. The oily solutions are suitable for intra-articular, intra-muscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is readily accomplished by standard pharmaceutical techniques well-known to those skilled in the art. Additionally, it is also possible to administer the compounds of the present invention topically when treating inflammatory conditions of the skin and this may preferably be done by way of creams, jellies, gels, pastes, ointments and the like, in accordance with standard pharmaceutical practice.
The compounds of formula (I) may also be administered in the form of suppositories for rectal or vaginal administration of the active ingredient. These compositions can be prepared by mixing the active ingredient with a suitable non-irritating excipient which is solid at room temperature (for example, 10xc2x0 C. to 32xc2x0 C.) but liquid at the rectal temperature and will melt in the rectum or vagina to release the active ingredient. Such materials are polyethylene glycols, cocoa butter, suppository and wax.
For buccal administration, the composition may take the form of tablets or lozenges formulated in conventional manner.
Combination With Other Drugs:
Compounds of Formula I would be useful for, but not limited to, the treatment of inflammation in a subject, and for treatment of other inflammation-associated disorders, such as, as an analgesic in the treatment of pain and headaches, or as an antipyretic for the treatment of fever. For example, combinations of the invention would be useful to treat arthritis, including but not limited to rheumatoid arthritis, spondyloarthopathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus and juvenile arthritis. Such combinations of the invention would be useful in the treatment of asthma, bronchitis, in menstrual cramps, tendinitis, bursitis, and skin related conditions such as psoriasis, eczema, burns and dermatitis. Combinations of the invention also would be useful to treat gastrointestinal conditions such as inflammatory bowel disease. Crohn""s disease, gastritis, irritable bowel syndrome and ulcerative colitis and for the prevention of colorectal cancer. Combinations of the invention would be useful in creating inflammation in such diseases as vascular diseases, migraine headaches, periarteritis nodosa, thyroiditis, aplastic anemia, Hodgkin""s disease, sclerodoma, rheumatic fever, type I diabetes, myasthenia gravis, multiple sclerosis, sarcoidosis, nephrotic syndrome, Behcet""s syndrome, polymyositis, gingivitis, hypersensitivity, Conjunctivitis, swelling occurring after injury, myocardial ischemia, and the like. The combinations would also be useful for the treatment of certain central nervous system disorders such as Alzheimer""s disease and dimentia. The combinations of the invention are useful as anti-inflammatory agents, such as for the treatment of arthritis, with the additional benefit of having significantly less harmful side effects. These compositions would also be useful in the treatment of allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, atherosclerosis and central nervous system damage resulting from stroke, ischemia and trauma.
Compounds of formula (I) will be useful as a partial or complete substitute for conventional NSAID""s in preparations wherein they are presently co-administered with other agents or ingredients. Thus, the invention encompasses pharmaceutical compositions for treating COX-2 mediated diseases as defined above comprising a non-toxic therapeutically effective amount of the compound of formula (I) and one or more ingredients such as another pain reliever including acetaminophen or phenacetin; a potentiator including caffeine; an H2-antagonist, aluminom or magnesium hydroxide, simethicone, a decongestant including phenylephrine, phenylproanolamine, psuedophedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, or levodesoxyephedrine; an antiitussive including codeine, hydrocodone, caramiphen, carbetapentane, or dextramethorphan; a prostaglandin including misoprostol, enprostil, rioprostil, ornoprotol or rosaprostol; a diuretic; a sedating or non-sedating antihistamine; anticancer agents such as angiostatin and endostatin; anti-Alzheimers such as Doepezil and Tacrine hydrochloride; and TNF alpha inhibitors such as Etanercept.
These cyclooxygenase inhibitors can further be used in combination with a nitric oxide inhibitors disclosed in WO 96/28145.
Also, the invention encompasses pharmaceutical compositions for treating COX-2 mediated diseases as defined above comprising a non-toxic therapeutically effective amount of the compound of formula (I) and one or more anti-ulcer agent and/or prostaglandins, which are disclosed in WO 97/11701.
The useful prostaglandins include misoprostol, plus-minus methyl 11xcex1,16-dihydroxy-16-methyl-9-oxoprost 13E-en-1-oate; enisoprost and methyl-7-[2B-[6-(1-cyclopenten-1-yl)-4-hydroxy-4-methyl-1E, 5E-hexadienyl]-3xcex1-hydroxy-5-oxo 1R,1xcex1-cyclopentyl]-4Z-heptenoate. Prostaglandins within the scope of the invention also include arbaprostil, enprostil, rioprostol, nocloprost, mexiprostil, ornoprostol, dimoxaprost, tiprostanide and rosaprostol.
The present compounds may also be used in co-therapies, partially or completely, in place of other conventional antiinflammatories, such as together with steroids, 5-lipoxygenase inhibitors, LTB4 antagonists and LTA4 hydrolase inhibitor""s.
An example of LTB4 is disclosed in WO97/29774. Suitable LTB4 inhibitors include, among others, ebselen, Bayer Bay-x-1005, Ciba Geigy compound CGS-25019C, Leo Denmark compound ETH-615, Lilly compound LY-293111, Ono compound ONO4057, Terumo compound TMK-688, Lilly compounds LY-213024, 264086 and 292728, Ono compound ONO-LB457, Searle compound SC-S3228, calcitrol, Lilly compounds LY-210073, LY223982, LY233469, and LY255283, Ono compound ONO-LB-448, Searle compounds SC-41930, SC-50605 and SC-51146, and SKandF compound SKF-104493. Preferably, the LTB4 inhibitors are selected from ebselen, Bayer Bay-x-1005, Ciba Geigy compound CGS-25019C, Leo Denmark compound ETH-61S, Lilly compound LY-293111, Ono compound ONO-4057 and Terumo compound TMK-688.
An example of 5-LO inhibitors is disclosed in WO97/29776. Suitable 5-LO inhibitors include, among others, masoprocol, tenidap, zileuton, pranlukast, tepoxalin, rilopirox, flezelastine hydrochloride, enazadrem phosphate and bunaprolast.
An example of LTA4 hydrolase inhibitors is disclosed in WO97/29774. Suitable LTA4 hydrolase inhibitors include, among others, Rhone-Poulenc Rorer RP-64966.
The administration of the present invention may be for either prevention or treatment purposes. The methods and compositions used herein may be used alone or in conjunction with additional therapies known to those skilled in the art in the prevention or treatment of angiogenesis. Alternatively, the methods and compositions described herein may be used as adjunct therapy. By way of example, the cyclooxygenase-2 inhibitor may be administered alone or in conjunction with other antineoplastic agents or other growth inhibiting agents or other drugs or nutrients.
There are large numbers of antineoplastic agents available in commercial use, in clinical evaluation and in pre-clinical development, which could be selected for treatment of angiogenesis by combination drug chemotherapy. Such antineoplastic agents fall into several major categories, namely, antibiotic-type agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents and a category of miscellaneous agents. Alternatively, other anti-neoplalstic agents, such as metallomatrix proteases inhibitors (MMP), such as MMP-13 inhibitors including batiastat, marimastat. Agouron Pharmaceuticals AG-3340, and Roche R0-32-3555, or alpha,beta,inhibitors may be used.
A first family of antineoplastic agents which may be used in combination with a selective cyclooxygenase-2 inhibitor consists of antimetabolite-type antineoplastic agents. Suitable antimetabolite antineoplastic agents may be selected from the group consisting of 5-FU-fibrinogen, acanthifolic acid, aminothiadiazole, brequinar sodium, carmoftir, Ciba-Geigy CGP-30694, cyclopentyl cytosine, cytarabine phosphate stearate, cytarabine conjugates, Lilly DATHF, Merrel Dow DDFC, dezaguanine, dideoxycytidine, dideoxyguanosine, didox, Yoshitomi DMDC, doxifluridine, Wellcome EHNA, Merck and Co. EX-015, fazarabine, floxuridine, fludarabine phosphate, 5-fluorouracil, N-(2xe2x80x2-furanidyl)-5-fluorouracil, Daiichi Seiyaku F0-152, isopropyl pyrrolizine, Lilly LY-188011, Lilly LY-264618, methobenzaprim, methotrexate, Wellcome MZPES. norspermidine, NCI NSC-127716, NCI NSC-264880, NCI NSC-39661, NCI NSC-612567, Warner-Lambert PALA, pentostatin, piritrexim, plicamycin, Asahi Chemical PL-AC, Takeda TAC-788, thioguanine, tiazofurin, Erbamont TIF, trimetrexate, tyrosine kinase inhibitors, tyrosine protein kinase inhibitors, Taiho UFT and uricytin.
A second family of antineoplastic agents which may be used in combination with a selective cyclooxygenase-2 inhibitor consists of alkylating-type antineoplastic agents. Suitable alkylating-type antineoplastic agents may be selected from the group consisting of Shionogi 254-S, aldo-phosphamide analogues, altretamine, anaxirone, Boehringer Mannheim BBR-2207, bestrabucil, budotitane, Wakunaga CA-102, carboplatin, carmustine, Chinoin-139, Chinoin-153, chlorambucil, cisplatin, cyclophosphamide, American Cyanamid CL-286558, Sanofi CY-233, cyplatate, Degussa D-19-384, Sumimoto DACHP(Myr)2, diphenylspiromustine, diplatinum cytostatic. Erba distamycin derivatives, Chugai DWA-2114R, ITI E09, elmustine, Erbamont FCE-24517, estramustine phosphate sodium, fotemustine, Unimed G-6-M, Chinoin GYKI-17230, hepsul-fam, ifosfamide, iproplatin, lomustine, mafosfamnide, mitolactol, Nippon Kayaku NK-121, NCI NSC-264395, NCI NSC-342215, oxaliplatin, Upjohn PCNU, prednimustine, Proter PTT-119, ranimustine, semustine, SmithKline SKandF-101772, Yakult Honsha SN-22, spiromus-tine, Tanabe Seiyaku TA-077, tauromustine, temozolomide, teroxirone, tetraplatin and trimelamol.
A third family of antineoplastic agents which may be used in combination with a selective cyclooxygenase-2 inhibitor consists of antibiotic-type antineoplastic agents. Suitable antibiotic-type antineoplastic agents may be selected from the group consisting of Taiho 4181-A, aclarubicin, actinomycin D, actinoplanone, Erbamont ADR-456, aeroplysinin derivative, Ajinomoto AN-201-II. Ajinomoto AN-3, Nippon Soda anisomycins, anthracycline, azino-mycin-A, bisucaberin, Bristol-Myers BL-6859, Bristol-Myers BMY-25067. Bristol-Myers BMY-25551, Bristol-Myers BMY-26605, Bristol-Myers BMY-27557, Bristol-Myers BMY-28438, bleomycin sulfate, bryostatin-1, Taiho C-1027, calichemycin, chromoximycin, dactinomycin, daunorubicin, Kyowa Hakko DC-102, Kyowa Hakko DC-79, Kyowa Hakko DC-88A, Kyowa Hakko DC89-A1, Kyowa Hakcko DC92-B, ditrisarubicin B, Shionogi DOB-41, doxorubicin, doxorubicin-fibrinogen, elsamicin-A, epirubicin, erbstatin, esorubicin, esperamicin-A1, esperamicin-A1b. Erbamont FCE-21954, Fujisawa FK-973, fostriecin, Fujisawa FR-900482, glidobactin, gregatin-A, grincamycin, herbimycin, idarubicin, illudins, kazusamycin, kesarirhodins, Kyowa Hakko KM-5539, Kirin Brewery KRN-8602, Kyowa Hakko KT-5432, Kyowa Hakko KT-5594, Kyowa Hakko KT-6149, American Cyanamid LL-D49194, Meiji Seika ME 2303, menogaril, mitomycin, mitoxantrone, SmithKline M-TAG, neoenactin, Nippon Kayaku NK-313, Nippon Kayaku NKT-O1, SRI International NSC-357704, oxalysine, oxaunomycin, peplomycin, pilatin, pirarubicin, porothramycin, pyrindamycin A, Tobishi RA-I, rapamycin, rhizoxin, rodorubicin, sibanomicin, siwenmycin, Sumitomo SM-5887, Snow Brand SN-706, Snow Brand SN-07, sorangicin-A, sparsomycin, SS Pharmaceutical SS-21020, SS Pharmaceutical SS-7313B, SS Pharmaceutical SS-9816B, steffimycin B, Taiho 4181-2, talisomycin, Takeda TAN-868A, terpentecin, thrazine, tricrozarin A, Upjohn U-73975, Kyowa Hakko UCN-10028A, Fujisawa WF-3405, Yoshitomi Y-2S024 and zorubicin.
A fourth family of antineoplastic agents which may be used in combination with the selective cyclooxygenase-2 inhibitor consists of a miscellaneous family of antineoplastic agents selected from the group consisting of alpha-carotene, alpha-difluoromethyl-arginine, acitretin, Biotec AD-5, Kyorin AHC-52, alstonine, amonafide, amphethinile. arnsacrine, Angiostat, ankinomycin, anti-neoplaston AIO, antineoplaston A2, antineoplaston A3, antineoplaston A5, antineoplaston AS2-1, Henkel APD, aphidicolin glycinate, asparaginase, Avarol, baccharin, batracylin, benfluron, benzotript, Ipsen-Beaufour BIM-23015, bisantrene. Bristo-Myers BMY-40481, Vestar boron-1O, bromofosfamide, Wellcome BW-502, Wellcome BW-773, caracemide, carmethizole hydrochloride, Ajinomoto CDAF, chlorsulfaquinoxalone, Chemes CHX-2053, Chemex CHX-1OO, Warner-Lambert CI-921, Warner-Lambert CI-937, Warner-Lambert CI-941, Warner-Lambert CI-958, clanfenur, claviridenone, ICN compound 1259, ICN compound 4711, Contracan, Yakult Honsha CPT-11, crisnatol, curaderm, cytochalasin B, cytarabine, cytocytin, Merz D-609, DABIS maleate, dacarbazine, datelliptinium, didemnin-B, dihaematoporphyrin ether, dihydrolenperone, dinaline, distamycin, Toyo Pharmnar DM-341, Toyo Pharmar DM-75, Daiichi Seiyaku DN-9693, elliprabin, elliptinium acetate, Tsumura EPMTC, ergotamine, etoposide, etretinate, fenretinide, Fujisawa FR-57704, gallium nitrate, genkwadaphnin, Chugai GLA43, Glaxo GR-63178, grifolan NMF-5N, hexadecylphosphocholine, Green Cross HO-221, homoharringtonine, hydroxyurea, BTG ICRF-187, ilmofosine, isoglutamine, isotretinoin. Otsuka JI-36, Ramot K-477, Otsuak K-76COONa, Kureha Chemical K-AM, MECT Corp KI-8110, American Cyanamid L-623, leukoregulin, lonidamine, Lundbeck LU-23-112, Lilly LY-186641, NCI (US) MAP, marycin, Merrel Dow MDL-27048, Medco MEDR-340, merbarone, merocyanine derivatives, methylanilinoacridine, Molecular Genetics MGI-136, minactivin, mitonafide, mitoquidone, mopidamol, motretinide, Zenyaku Kogyo MST-16, N-(retinoyl)amino acids, Nisshin Flour Milling N-021, N-acylated-dehydroalanines, nafazatrom, Taisho NCU-190, nocodazole derivative, Normosang, NCI NSC-145813, NCI NSC-361456, NCI NSC-604782, NCI NSC-95580, octreotide, Ono ON0-112, oquizanocine, Akzo Org-10172, pancratistatin, pazelliptine, Warner-Lambert PD-111707, Warner-Lambert PD-115934, Warner-Lambert PD-131141, Pierre Fabre PE-1OO1, ICRT peptide D, piroxantrone, polyhaematoporphyrin, polypreic acid, Efamol porphyrin, probimane, procarbazine, proglurnide, Invitron protease nexin I, Tobishi RA-700, razoxane, Sapporo Breweries RBS, restrictin-P, retelliptine, retinoic acid, Rhone-Poulenc RP-49532, Rhone-Poulenc RP-56976, SmithKline SKandF-104864, Sumitomo SM-108, Kuraray SMANCS, SeaPharm SP-10094, spatol, spirocyclopropane derivatives, spirogermanium, Unimed, SS Pharmaceutical SS-554, strypoldinone, Stypoldione, Suntory SUN 0237, Suntory SUN 2071, superoxide dismutase, Toyama T-506, Toyama T-680, taxol, Teijin TEI-0303, teniposide, thaliblastine, Eastman Kodak TJB-29, tocotrienol, Topostin, Teijin TT-82, kyowa Hakko UCN-O1, Kyowa Hakko UCN-1028, ukrain, Eastman Kodak USB-006, vinblastine sulfate, vincristine, vindesine, vinestramide, vinorelbine, vintriptol, vinzolidine, withanolides and Yamanouchi YM-534.
Examples of radioprotective agents which may be used in the combination chemotherapy of this invention are AD-5, adchnon, amifostine analogues, detox, dimesna, 1-102, MN-159, N-acylated-dehydroalanines, TGF-Genentech, tiprotimod, amifostine, WR-1511327, FUT-187, ketoprofen transdermal, naburnetone, superoxide dismutase (Chiron) and superoxide disrrtutase Enzon.
Methods for preparation of the antineoplastic agents described above may be found in the literature. Methods for preparation of doxorubicin, for example, are described in U.S. Pat. Nos. 3,590,028 and No. 4,012,448. Methods for preparing metallomatrix protease inhibitors are described in EP 780386, WO97/20824. WO96/15096. Methods for preparing SOD mimics are described in EP 524,101. Methods for preparing alpha,beta, inhibitors are described in WO97/08174.
In addition, the selective COX-2 inhibitor may be administered in conjunction with other antiinflammatory agents for maximum safety and efficacy, including NSAID""s, selective COX-1 inhibitors and inhibitors of the leukotriene pathway, including 5-lipoxygenase inhibitors. Examples of NSAID""s include indomethacin, naproxen, ibruprofen, salicylic acid derivatives such as aspirin, diclofenac, ketorolac, piroxicam, meloxicam, mefenamic acid, sulindac, tolmetin sodium, zomepirac, fenoprofen, phenylbutazone, oxyphenbutazone, nimesulide, zaltoprofen and letodolac.
The activity of the compounds of the formula (I) of the present invention was demonstrated by the following assays.
Human Cell Based COX-1 Assay
Human peripheral blood obtained from healthy volunteers was diluted to 1/10 volume with 3.8% sodium citrate solution. The platelet-rich plasma immediately obtained was washed with 0.14 M sodium chloride containing 12 mM Tris-HCl (pH 7.4) and 1.2 mM EDTA. Platelets were then washed with platelet buffer (Hanks buffer (Ca free) containing 0.2% BSA and 20 mM Hepes). Finally, the human washed platelets (HWP) were suspended in platelet buffer at the concentration of 2.85xc3x97108 cells/ml and stored at room temperature until use. The HWP suspension (70 xcexcl aliquots, final 2.0xc3x97107 cells/ml) was placed in a 96-well U bottom plate and 10 xcexcl aliquots of 12.6 mM CaCl2 added. Platelets were incubated with A23187 (final 10 xcexcM, Sigma) with test compound (0.1-100 xcexcM) dissolved in DMSO (final concentration; less than 0.01%) at 37xc2x0 C. for 15 min. The reaction was stopped by addition of EDTA (final 7.7 mM) and TxB2 in the supernatant quantitated by using a radioimmunoassay kit (Amersham) according to the manufacturer""s procedure.
Human Cell Based COX-2 Assay
Inhibition of COX-2 Activity After Induction of COX-2 by hIL-1xcex2
The human cell based COX-2 assay was carried out as previously described (Moore et al., Inflam. Res., 45, 54, 1996). Confluent human umbilical vein endothelial cells (HUVECs, Morinaga) in a 96-well U bottom plate were washed with 100 xcexcl of RPMI1640 containing 2% FCS and incubated with hIL-1xcex2 (final concentration 300 U/ml, R and D Systems) at 37xc2x0 C. for 24 hr. After washing, the activated HUVECs were stimulated with A23187 (final concentration 30 xcexcM) in Hanks buffer containing 0.2% BSA, 20 mM Hepes and test compound (0.1 nM-100 xcexcM) dissolved in DMSO (final concentration; less than 0.01%) at 37xc2x0 C. for 15 min. 6-Keto-PGF1xcex1, stable metabolite of PGI2, in the supernatant was quantitated after adequate dilution by using a radioimmunoassay kit (Amersham) according to the manufacturer""s procedure.
Inhibition of COX-2 During the Induction Phase
Confluent human umbilical vein endothelial cells (HUVECs, Morinaga) in a 96-well U bottom plate were washed with 100 xcexcl of RPMI1640 containing 2% FCS and test compound (0.1 nM-100 xcexcM) dissolved in DMSO (final concentration; less than 0.01%), and incubated with hIL-1xcex2 (final concentration 300 U/ml, R and D Systems) at 37xc2x0 C. for 24 hr. After washing, the HUVECs were stimulated with A23187 (final concentration 30 xcexcM) in Hanks buffer containing 0.2% BSA and 20 mM Hepes at 37xc2x0 C. for 15 min. 6-Keto-PGF1xcex1, a stable metabolite of PGI2, in the supernatant was quantitated after adequate dilution by using a radioimmunoassay kit (Amersham) according to the manufacturer""s procedure.
Carrageenan Induced Foot Edema in Rats
Male Sprague-Dawley rats (5 weeks old, Charles River Japan) were fasted overnight. A line was drawn using a marker above the ankle on the right hind paw and the paw volume (V0) was measured by water displacement using a plethysmometer (Muromachi). Animals were given orally either vehicle (0.1% methyl cellulose or 5% Tween 80) or a test compound (2.5 ml per 100 g body weight). One hour later, the animals were then injected intradermally with xcex-carrageenan (0.1 ml of 1% w/v suspension in saline, Zushikagaku) into right hind paw (Winter et al., Proc. Soc. Exp. Biol. Med., 111, 544, 1962; Lombardino et al., Arzneim. Forsch., 25, 1629, 1975) and three hours later, the paw volume (V3) was measured and the increase in volume (V3-V0) calculated. Since maximum inhibition attainable with classical NSAIDs is 60-70%, ED30 values were calculated.
Gastric Ulceration in Rats
The gastric ulcerogenicity of test compound was assessed by a modification of the conventional method (Ezer et al., J. Pharm. Pharmacol., 28, 655, 1976; Cashin et al., J. Pharm. Pharmacol., 29, 330-336, 1977). Male Sprague-Dawley rats (5 weeks old, Charles River Japan), fasted overnight, were given orally either vehicle (0.1% methyl cellulose or 5% Tween 80) or a test compound (1 ml per 100 g body weight). Six hours after, the animals were sacrificed by cervical dislocation. The stomachs were removed and inflated with 1% formalin solution (10 ml). Stomachs were opened by cutting along the greater curvature. From the number of rats that showed at least one gastric ulcer or haemorrhaging erosion (including ecchymosis), the incidence of ulceration was calculated. Animals did not have access to either food or water during the experiment.
Statistical program packages, SYSTAT (SYSTAT, INC.) and StatView (Abacus Cencepts, Inc.) for Macintosh were used. Differences between test compound treated group and control group were tested for using ANOVA. The IC50 (ED30) values were calculated from the equation for the log-linear regression line of concentration (dose) versus percent inhibition.
Some compounds prepared in the Working Examples as described herein after were tested by these methods, and showed IC50 values of 0.001 xcexcM to 10 xcexcM with respect to inhibition of COX-2.
Also, the above-mentioned most preferred compounds were tested by these methods, and showed IC50 values of 0.001 xcexcM to 0.5 xcexcM with respect to inhibition of COX-2.
COX-2 selectivity can be determined by ratio in terms of IC50 value of COX-1 inhibition to COX-2 inhibition. In general, it can be said that a compound showing a COX-1/COX-2 inhibition ratio of more than 2 has good COX-2 selectivity.
Some compounds prepared in Examples showed COX-1/COX-2 inhibition ratio of more than 10.